Each of pyridoxine, pyridoxal, and pyridoxamine is a substance having vitamin B6 action, and referred to as a class of vitamin B6 together with each 5′-phosphate thereof, i.e., pyridoxine 5′-phosphate, pyridoxal 5′-phosphate, and pyridoxamine 5′-phosphate. These compounds are metabolized to give pyridoxal 5′-phosphate in vivo, and play an important role as a coenzyme for enzymes involved in amino acid metabolism.
It is known that pyridoxine and hydrochloride thereof are extremely unstable to light, and similarly, pyridoxal, pyridoxamine, and pyridoxal 5′-phosphate are also very unstable to light. For this reason, it is desired to provide a compound of the vitamin B6 class that has improved light stability.
Several vitamin B6 glycosides in which vitamin B6 is glycosylated have been reported. For example, pyridoxine 5′-β-D-glucoside exists in plant bodies. However, light stability thereof has not been reported. Vitamin B6 glycosides glycosylated at the 4′- or 5′-position (pyridoxine 4′-α-D-glucoside, pyridoxine 5′-α-D-glucoside) were enzymatically synthesized (for example, J. Vitaminol., 15, pp. 160-166, 1969; and Methods in Enzymology, 280, pp. 66-71, 1997). As for the stability of pyridoxine 4′-α-D-glucoside, and pyridoxine 5′-α-D-glucoside, it has been reported that these substances have superior long term stability at 50° C. in pharmaceutical preparations compared with pyridoxine hydrochloride (for example, Japanese Patent Unexamined Publication (KOKAI) Nos. 2002-265316 and 2002-265368). As for light stability, it has been reported that light stability of a mixture of pyridoxine 4′-α-D-glucoside and pyridoxine 5′-α-D-glucoside is improved compared with pyridoxine hydrochloride under an ultraviolet lamp irradiation test (for example, J. Vitaminol., 17, pp. 121-124, 1971). However, the reported stability is not sufficient for practical applications. No compound has been reported so far in which vitamin B6 is glycosylated at the 3-position and esterified into phosphoric acid ester.
It is known that light stability of vitamin B6 is improved by addition of boric acid (Vitamins, 22, pp. 138-141, 1961) or addition of a sugar alcohol (Japanese Patent Unexamined Publication (KOKAI) No. 07-206664). However, the effect is not satisfactory, and moreover, a problem arises that the use is limited by the addition of boric acid or a sugar alcohol.
It is known that when vitamin B6 is mixed with other class of vitamins, decomposition of the other vitamins may sometimes be accelerated. For example, it has been reported that when calcium pantothenate and vitamin B6 are mixed and stored at 40° C. under 75% RH, decomposition of calcium pantothenate is accelerated (Katei-yaku Kenkyu (Home Remedy Research), 54(5), pp. 54-58, 1986). It is known that in an aqueous solution added with boric acid, both of vitamin B6 and pantothenic acid can stably exist (Japanese Patent Unexamined Publication (KOKAI) No. 05-17355). However, the effect is not satisfactory, and a problem arises that the use is limited by the addition of boric acid.
Vitamin B6 is a vitamin that plays an important role for protein metabolism in vivo, and also acts as a coenzyme in metabolism of fats. Shortage of vitamin causes skin inflammation, swelling, psilosis and the like (Fragrance Journal, 17 (3), 96-100 (1986); Japanese Patent Unexamined Publication (KOKAI) No. 2002-265368). As dermal external preparations, external preparations added with a vitamin B6 derivative such as pyridoxine hydrochloride have conventionally been used for relief of skin roughness, pimple, sun tanning, and hot flush by snow burning, therapeutic and prophylactic treatments of itching due to inflammation, dandruff due to seborrhea sicca and the like. However, vitamin B6 derivatives conventionally used have problems that they have poor light stability, and decomposition products thereof cause skin irritation and the like. They also have a problem that sufficient effects as vitamin B6 cannot be obtained when they are added and used in skin external preparations.